Loviscach M, Rehman N, Carter L, Mudaliar S, Mohadeen P, Ciaraldi T P, Veerkamp J H, Henry R R
VA San Diego Healthcare System, California 92161, USA.
Diabetologia. 2000 Mar;43(3):304-11. doi: 10.1007/s001250050048.
AIMS/HYPOTHESIS: To evaluate the tissue distribution and possible role of the peroxisome proliferator-activated receptors (PPARs) in insulin action in fat and muscle biopsy specimens from lean, obese and subjects with Type II (non-insulin-dependent) diabetes mellitus.
We measured PPAR alpha, PPAR beta (delta) and PPAR gamma protein expression by western blot analysis. The PPAR gamma protein was also measured in muscle before and after 3-h hyperinsulinaemic (300 mU.m-2.min-1) euglycaemic clamps.
The PPAR alpha protein was expressed preferentially in muscle relative to fat (more than sevenfold). The PPAR beta protein was similar in fat and muscle. The amount of PPAR gamma protein found in muscle was, on average, two-thirds of that present in fat. There was no statistically significant difference between non-diabetic and diabetic subjects in baseline (preclamp) muscle PPAR (alpha, beta or gamma) protein expression. Subgroup analysis showed, however, significantly higher PPAR gamma protein in the most insulin resistant diabetic subjects with glucose disposal rates of 3-6 mg.kg-1.min-1 compared with their age and weight matched counterparts with glucose disposal rates of 6-9 (147 +/- 23 vs 88 +/- 10 AU/microgram protein, p < or = 0.01 in diabetic and vs 94 +/- 15, p < or = 0.04 in non-diabetic subjects). Muscle PPAR gamma protein and glucose disposal rates were inversely correlated in diabetic subjects (r = -0.47, p < or = 0.05).
CONCLUSION/INTERPRETATION: All PPARs (alpha, beta or gamma) are present in skeletal muscle and adipose tissue with different relative distributions. The PPAR gamma protein is abundant in skeletal muscle as well as adipose tissue. The altered expression of skeletal muscle PPAR gamma is consistent with a role for this nuclear protein in the impaired insulin action of Type II diabetes.
目的/假设：评估过氧化物酶体增殖物激活受体（PPARs）在来自瘦人、肥胖者及II型（非胰岛素依赖型）糖尿病患者的脂肪和肌肉活检标本中的组织分布及其在胰岛素作用中的可能作用。
我们通过蛋白质印迹分析测量PPARα、PPARβ（δ）和PPARγ蛋白表达。还在3小时高胰岛素血症（300 mU·m⁻²·min⁻¹）正常血糖钳夹前后测量肌肉中的PPARγ蛋白。
PPARα蛋白在肌肉中的表达相对于脂肪优先表达（超过7倍）。PPARβ蛋白在脂肪和肌肉中相似。肌肉中发现的PPARγ蛋白量平均为脂肪中的三分之二。非糖尿病和糖尿病患者在基线（钳夹前）肌肉PPAR（α、β或γ）蛋白表达上无统计学显著差异。然而，亚组分析显示，与年龄和体重匹配、葡萄糖处置率为6 - 9的对应者相比，葡萄糖处置率为3 - 6 mg·kg⁻¹·min⁻¹的胰岛素抵抗最严重的糖尿病患者中PPARγ蛋白显著更高（糖尿病患者中为147±23 vs 88±10 AU/μg蛋白，p≤0.01；非糖尿病患者中为94±15，p≤0.04）。糖尿病患者中肌肉PPARγ蛋白与葡萄糖处置率呈负相关（r = -0.47，p≤0.05）。
结论/解读：所有PPARs（α、β或γ）都存在于骨骼肌和脂肪组织中，具有不同的相对分布。PPARγ蛋白在骨骼肌和脂肪组织中都很丰富。骨骼肌PPARγ表达的改变与该核蛋白在II型糖尿病胰岛素作用受损中的作用一致。
